Mutation Research-Reviews in Mutation Research最新文献

{"title":"A comparison between mutational profiles in tumour tissue DNA and circulating tumour DNA in head and neck squamous cell carcinoma – A systematic review","authors":"Xiaomin Huang ,&nbsp;Paul Leo ,&nbsp;Lee Jones ,&nbsp;Pascal H.G. Duijf ,&nbsp;Gunter Hartel ,&nbsp;Lizbeth Kenny ,&nbsp;Sarju Vasani ,&nbsp;Chamindie Punyadeera","doi":"10.1016/j.mrrev.2023.108477","DOIUrl":"10.1016/j.mrrev.2023.108477","url":null,"abstract":"<div><h3>Background</h3><p>Head and neck cancer is the seventh most common malignancy globally. Head and neck squamous cell carcinoma (HNSCC) originates from squamous cells and 90% of HNC are HNSCC. The gold standard for diagnosing HNSCC is tissue biopsy. However, given tumour heterogeneity, biopsies may miss important cancer-associated molecular signatures, and more importantly, after the tumour is excised, there is no means of tracking response to treatment in patients. Captured under liquid biopsy, circulating tumour DNA (ctDNA), may identify in vivo molecular genotypes and complements tumour tissue analysis in cancer management. A systematic search was conducted in PubMed, Embase, Scopus and the Cochran Library between 2012 to early 2023 on ctDNA in HNSCC using publications written in English. We summarise 20 studies that compared mutational profiles between tumour tissue DNA (tDNA) and ctDNA, using a cohort of 631 HNSCC patients and 139 controls. Among these studies, the concordance rates varied greatly and the most mutated and the most concordant gene was <em>TP53,</em> followed by <em>PIK3CA, CDKN2A, NOTCH1</em> and <em>FAT1.</em> Concordant variants were mainly found in Stage IV tumours, and the mutation type is mostly single nucleotide variants (SNV). We conclude that, as a biomarker for HNSCC, ctDNA demonstrates great promise as it recapitulates tumour genotypes, however additional multi-central trials are needed.</p></div>","PeriodicalId":49789,"journal":{"name":"Mutation Research-Reviews in Mutation Research","volume":"793 ","pages":"Article 108477"},"PeriodicalIF":5.3,"publicationDate":"2023-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S138357422300025X/pdfft?md5=0b2d2421aae7730b8caf91d704d5628a&pid=1-s2.0-S138357422300025X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136400048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Next-generation sequencing methodologies to detect low-frequency mutations: “Catch me if you can”","authors":"Vijay Menon ,&nbsp;Douglas E. Brash","doi":"10.1016/j.mrrev.2023.108471","DOIUrl":"10.1016/j.mrrev.2023.108471","url":null,"abstract":"<div><p><span>Mutations, the irreversible changes in an organism’s DNA sequence, are present in tissues at a variant allele frequency (VAF) ranging from ∼10</span>^-8 per bp for a founder mutation to ∼10^-3<span> for a histologically normal tissue sample containing several independent clones – compared to 1%− 50% for a heterozygous tumor mutation or a polymorphism. The rarity of these events poses a challenge for accurate clinical diagnosis and prognosis, toxicology, and discovering new disease etiologies. Standard Next-Generation Sequencing (NGS) technologies report VAFs as low as 0.5% per nt, but reliably observing rarer precursor events requires additional sophistication to measure ultralow-frequency mutations. We detail the challenge; define terms used to characterize the results, which vary between laboratories and sometimes conflict between biologists and bioinformaticists; and describe recent innovations to improve standard NGS methodologies including: single-strand consensus sequence methods such as Safe-SeqS and SiMSen-Seq; tandem-strand consensus sequence methods such as o2n-Seq and SMM-Seq; and ultrasensitive parent-strand consensus sequence methods such as DuplexSeq, PacBio HiFi, SinoDuplex, OPUSeq, EcoSeq, BotSeqS, Hawk-Seq, NanoSeq, SaferSeq, and CODEC. Practical applications are also noted. Several methods quantify VAF down to 10</span>^-5 at a nt and mutation frequency (MF) in a target region down to 10^-7 per nt. By expanding to &gt; 1 Mb of sites never observed twice, thus forgoing VAF, other methods quantify MF &lt; 10^-9 per nt or &lt; 15 errors per haploid genome. Clonal expansion cannot be directly distinguished from independent mutations by sequencing, so it is essential for a paper to report whether its MF counted only different mutations – the minimum independent-mutation frequency MF_minI – or all mutations observed including recurrences – the larger maximum independent-mutation frequency MF_maxI which may reflect clonal expansion. Ultrasensitive methods reveal that, without their use, even mutations with VAF 0.5–1% are usually spurious.</p></div>","PeriodicalId":49789,"journal":{"name":"Mutation Research-Reviews in Mutation Research","volume":"792 ","pages":"Article 108471"},"PeriodicalIF":5.3,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10273450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mutagenesis-based plant breeding approaches and genome engineering: A review focused on tomato","authors":"Durre Shahwar ,&nbsp;Namju Ahn ,&nbsp;Donghyun Kim ,&nbsp;Wooseong Ahn ,&nbsp;Younghoon Park","doi":"10.1016/j.mrrev.2023.108473","DOIUrl":"10.1016/j.mrrev.2023.108473","url":null,"abstract":"<div><p><span>Breeding is the most important and efficient method for crop improvement involving repeated modification of the genetic makeup of a plant population over many generations. In this review, various accessible breeding approaches, such as conventional breeding and mutation breeding (physical and chemical </span>mutagenesis<span><span> and insertional mutagenesis), are discussed with respect to the actual impact of research on the economic improvement of tomato agriculture. Tomatoes are among the most economically important fruit crops consumed worldwide because of their high nutritional content and health-related benefits. Additionally, we summarize mutation-based mapping approaches, including Mutmap and MutChromeSeq, for the efficient mapping of several genes identified by random indel mutations that are beneficial for crop improvement. Difficulties and challenges in the adaptation of new genome editing techniques that provide opportunities to demonstrate precise mutations are also addressed. Lastly, this review focuses on various effective and convenient genome editing tools, such as RNA interference (RNAi), zinc finger </span>nucleases<span> (ZFNs), transcription activator-like effector nucleases (TALENs), and clustered regularly interspaced short palindromic repeats (CRISPR/Cas9), and their potential for the improvement of numerous desirable traits to allow the development of better varieties of tomato and other horticultural crops.</span></span></p></div>","PeriodicalId":49789,"journal":{"name":"Mutation Research-Reviews in Mutation Research","volume":"792 ","pages":"Article 108473"},"PeriodicalIF":5.3,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10273453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Error-corrected next generation sequencing – Promises and challenges for genotoxicity and cancer risk assessment","authors":"Francesco Marchetti ,&nbsp;Renato Cardoso ,&nbsp;Connie L. Chen ,&nbsp;George R. Douglas ,&nbsp;Joanne Elloway ,&nbsp;Patricia A. Escobar ,&nbsp;Tod Harper Jr ,&nbsp;Robert H. Heflich ,&nbsp;Darren Kidd ,&nbsp;Anthony M. Lynch ,&nbsp;Meagan B. Myers ,&nbsp;Barbara L. Parsons ,&nbsp;Jesse J. Salk ,&nbsp;Raja S. Settivari ,&nbsp;Stephanie L. Smith-Roe ,&nbsp;Kristine L. Witt ,&nbsp;Carole L. Yauk ,&nbsp;Robert Young ,&nbsp;Shaofei Zhang ,&nbsp;Sheroy Minocherhomji","doi":"10.1016/j.mrrev.2023.108466","DOIUrl":"10.1016/j.mrrev.2023.108466","url":null,"abstract":"<div><p>Error-corrected Next Generation Sequencing (ecNGS) is rapidly emerging as a valuable, highly sensitive and accurate method for detecting and characterizing mutations in any cell type, tissue or organism from which DNA can be isolated. Recent mutagenicity and carcinogenicity studies have used ecNGS to quantify drug-/chemical-induced mutations and mutational spectra associated with cancer risk. ecNGS has potential applications in genotoxicity assessment as a new readout for traditional models, for mutagenesis studies in 3D organotypic cultures, and for detecting off-target effects of gene editing tools. Additionally, early data suggest that ecNGS can measure clonal expansion of mutations as a mechanism-agnostic early marker of carcinogenic potential and can evaluate mutational load directly in human biomonitoring studies. In this review, we discuss promising applications, challenges, limitations, and key data initiatives needed to enable regulatory testing and adoption of ecNGS – including for advancing safety assessment, augmenting weight-of-evidence for mutagenicity and carcinogenicity mechanisms, identifying early biomarkers of cancer risk, and managing human health risk from chemical exposures.</p></div>","PeriodicalId":49789,"journal":{"name":"Mutation Research-Reviews in Mutation Research","volume":"792 ","pages":"Article 108466"},"PeriodicalIF":5.3,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10135638","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Towards prevention of aneuploidy-associated cellular senescence and aging: more questions than answers?","authors":"Micheline Kirsch-Volders ,&nbsp;Michael Fenech","doi":"10.1016/j.mrrev.2023.108474","DOIUrl":"10.1016/j.mrrev.2023.108474","url":null,"abstract":"<div><p>The aim of this review is to discuss how aneuploidy contributes to the aging process, and to identify plausible strategies for its prevention. After an overview of mechanisms leading to aneuploidy and the major features of cellular senescence, we discuss the link between (i) aneuploidy and cellular senescence; (ii) aneuploidy and aging; and (iii) cellular senescence and aging. We also consider (i) interactions between aneuploidy, micronuclei, cellular senescence and aging, (ii) the potential of nutritional treatments to prevent aneuploidy-associated senescence and aging, and (iii) knowledge and technological gaps. Evidence for a causal link between aneuploidy, senescence and aging is emerging. <em>In vitro</em>, aneuploidy accompanies the entry into cellular senescence and can itself induce senescence. How aneuploidy contributes in vivo to cellular senescence is less clear. Several routes depending on aneuploidy and/or senescence converge towards chronic inflammation, the major driver of unhealthy aging. Aneuploidy can induce the pro-inflammatory Senescence Associated Secretory Phenotype (SASP), either directly or as a result of micronucleus (MN) induction leading to leakage of DNA into the cytoplasm and triggering of the cGAS-STING pathway of innate immune response. A major difficulty in understanding the impact of aneuploidy on senescence and aging in vivo, results from the heterogeneity of cellular senescence in different tissues at the cytological and molecular level. Due to this complexity, there is at the present time no biomarker or biomarker combination characteristic for all types of senescent cells. In conclusion, a deeper understanding of the critical role aneuploidy plays in cellular senescence and aging is essential to devise practical strategies to protect human populations from aneuploidy-associated pathologies. We discuss emerging evidence, based on in vitro and in vivo studies, that adequate amounts of specific micronutrients are essential for prevention of aneuploidy in humans and that precise nutritional intervention may be essential to help avoid the scourge of aneuploidy-driven diseases.</p></div>","PeriodicalId":49789,"journal":{"name":"Mutation Research-Reviews in Mutation Research","volume":"792 ","pages":"Article 108474"},"PeriodicalIF":5.3,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1383574223000224/pdfft?md5=9be283859167d4e70ead757eaacb100e&pid=1-s2.0-S1383574223000224-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49693383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"WNT5A: a double-edged sword in colorectal cancer progression","authors":"Muhammad Tufail,&nbsp;Changxin Wu","doi":"10.1016/j.mrrev.2023.108465","DOIUrl":"10.1016/j.mrrev.2023.108465","url":null,"abstract":"<div><p><span>The Wnt signaling pathway is known to play a crucial role in cancer, and </span><span><em>WNT5A</em></span> is a member of this pathway that binds to the <span><em>Frizzled</em></span> (<em>FZD</em>) and <em>Receptor Tyrosine Kinase-Like Orphan Receptor</em> (<em>ROR</em>) family members to activate non-canonical Wnt signaling pathways. The <em>WNT5A</em><span> pathway is involved in various cellular processes<span>, such as proliferation, differentiation, migration, adhesion, and polarization. In the case of colorectal cancer (CRC), abnormal activation or inhibition of </span></span><em>WNT5A</em> signaling can lead to both oncogenic and antitumor effects. Moreover, <em>WNT5A</em> is associated with inflammation, metastasis, and altered metabolism in cancer cells. This article aims to discuss the molecular mechanisms and dual roles of <em>WNT5A</em> in CRC.</p></div>","PeriodicalId":49789,"journal":{"name":"Mutation Research-Reviews in Mutation Research","volume":"792 ","pages":"Article 108465"},"PeriodicalIF":5.3,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9922812","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Systematic review of comparative transcriptomic studies of cellular resistance to genotoxic stress","authors":"Z.B. Ismailov ,&nbsp;E.S. Belykh ,&nbsp;A.A. Chernykh ,&nbsp;A.M. Udoratina ,&nbsp;D.V. Kazakov ,&nbsp;A.V. Rybak ,&nbsp;S.N. Kerimova ,&nbsp;I.O. Velegzhaninov","doi":"10.1016/j.mrrev.2023.108467","DOIUrl":"10.1016/j.mrrev.2023.108467","url":null,"abstract":"<div><p><span><span><span>The development of resistance by tumor cells to various types of therapy is a significant problem that decreases the effectiveness of oncology treatments. For more than two decades, comparative transcriptomic<span> studies of tumor cells with different sensitivities to ionizing radiation and chemotherapeutic agents have been conducted in order to identify the causes and mechanisms underlying this phenomenon. However, the results of such studies have little in common and often contradict each other. We have assumed that a systematic analysis of a large number of such studies will provide new knowledge about the mechanisms of development of therapeutic resistance in tumor cells. Our comparison of 123 differentially expressed gene (DEG) lists published in 98 papers suggests a very low degree of consistency between the study results. Grouping the data by type of genotoxic agent and tumor type did not increase the similarity. The most frequently overexpressed genes were found to be those encoding the </span></span>transport protein </span>ABCB1<span> and the antiviral defense protein<span><span> IFITM1. We put forward a hypothesis that the role played by the overexpression of the latter in the development of resistance may be associated not only with the stimulation of proliferation, but also with the limitation of exosomal communication and, as a result, with a decrease in the </span>bystander effect. Among down regulated DEGs, </span></span></span><span><em>BNIP3</em></span> was observed most frequently. The expression of <em>BNIP3</em>, together with <span><em>BNIP3L</em></span>, is often suppressed in cells resistant to non-platinum genotoxic chemotherapeutic agents, whereas it is increased in cells resistant to ionizing radiation. These observations are likely to be mediated by the binary effects of these gene products on survival, and regulation of apoptosis and autophagy. The combined data also show that even such obvious mechanisms as inhibition of apoptosis and increase of proliferation are not universal but show multidirectional changes.</p></div>","PeriodicalId":49789,"journal":{"name":"Mutation Research-Reviews in Mutation Research","volume":"792 ","pages":"Article 108467"},"PeriodicalIF":5.3,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10169123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ecogenotoxicity assessment with land snails: A mini-review","authors":"Maxime Louzon ,&nbsp;Annette de Vaufleury ,&nbsp;Nicolas Capelli","doi":"10.1016/j.mrrev.2023.108472","DOIUrl":"10.1016/j.mrrev.2023.108472","url":null,"abstract":"<div><p><span><span>In the context of the increasing environmental and sanitary crisis, it is accepted that soil pollution can cause health alterations and disturb natural population dynamics. Consequently, the assessment of the genotoxic potential of compounds found in contaminated soils is important. Indeed, the alteration of genomic integrity may increase the risk of cancer development and may impair reproduction and long-term population dynamics. Among the methodologies to assess terrestrial genotoxic potential, there has been growing interest during the last decade in monitoring alterations of the genome in bioindicators of soil quality. As some land snail species are recognized bioindicators of soil quality, especially to assess the environmental and toxicological </span>bioavailability of compounds, this review focuses on current knowledge regarding the genotoxicology of land snails. Classical biomarkers to assess genotoxic effects have been used (</span><em>e.g.,</em><span> DNA breakage, micronuclei, random amplification polymorphic DNA) at various stages of the life cycle, including embryos. The studies were performed </span><em>in vitro</em>, <em>in vivo</em>, <em>in situ</em> and <em>ex situ</em> and covered a diverse set of contaminants (nanoparticles, metal(loid)s, pesticides, polycyclic aromatic hydrocarbons) and snail species (<em>Cantareus aspersus</em>, <em>Eobania vermiculata</em>, <em>Theba pisana, Helix lucorum</em><span><span>). Based on recent studies reviewed here, the use of land snails to map soil genotoxic potential is promising due to their ability to reveal pollution and subsequent environmental risks. Moreover, the position of snails in the trophic chain and the existing bridges between contaminant bioavailability to snails and </span>bioaccessibility to humans reinforce the value of land snail-based ecotoxicological assessment.</span></p></div>","PeriodicalId":49789,"journal":{"name":"Mutation Research-Reviews in Mutation Research","volume":"792 ","pages":"Article 108472"},"PeriodicalIF":5.3,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10256621","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of C677T and A1298C polymorphisms of the MTHFR gene with maternal risk for Down syndrome: A meta-analysis of case-control studies","authors":"Carla Talita Azevedo Ginani ,&nbsp;Jefferson Romáryo Duarte da Luz ,&nbsp;Kleyton Santos de Medeiros ,&nbsp;Ayane Cristine Alves Sarmento ,&nbsp;Fabio Coppedè ,&nbsp;Maria das Graças Almeida","doi":"10.1016/j.mrrev.2023.108470","DOIUrl":"10.1016/j.mrrev.2023.108470","url":null,"abstract":"<div><h3>Background</h3><p><span><span>Several studies around the world support the hypothesis that genetic polymorphisms involved in </span>folate metabolism could be related to the maternal risk for Down syndrome (DS). Most of them investigated the role of </span><span><em>MTHFR</em></span> C677T and/or A1298C polymorphisms as maternal risk factors for DS, but their results are often conflicting and still inconclusive.</p></div><div><h3>Methods</h3><p>We conducted a systematic review and meta-analysis to clarify the association of <em>MTHFR</em> C677T and/or A1298C polymorphisms with the maternal risk of DS. Our search strategy selected 42 eligible case control studies for a total of 4131 case mothers and 5452 control mothers. The Newcastle–Ottawa Scale was used to assess the methodological quality of the selected studies. To assess the confidence of statistically significant associations we applied false positive report probability test, and we performed the trial sequential analysis to minimize the type I error and random error.</p></div><div><h3>Results</h3><p>We observed significant associations between the <em>MTHFR</em><span> C677T polymorphism and maternal risk for DS for each of the genetic models investigated (dominant, recessive, codominant, and allelic contrast). Subgroup analysis by region revelated significant association in the Asian population for all the genetic models investigated. Significant associations were also found for certain genetic models in North American, South American, and Middle Eastern populations, while no association was observed in Europeans. The </span><em>MTHFR</em> A1298C polymorphism did not show any association with the maternal risk of DS, either alone or in combination with the C677T one. The results of false positive report probability to verify the confidence of a significant association suggest that the association between the <em>MTHFR</em> C677T polymorphism and the maternal risk for DS is noteworthy, with high confidence in Asians.</p></div><div><h3>Conclusion</h3><p>The results of this meta-analysis support that the <em>MTHFR</em> C677T polymorphism, but not the A1298C one, is associated with the maternal risk for DS. Further studies are required to better characterize the contribution of gene-gene and gene-nutrient interactions as well as those of other regional or ethnic factors that could explain the observed different effect size in different populations.</p></div>","PeriodicalId":49789,"journal":{"name":"Mutation Research-Reviews in Mutation Research","volume":"792 ","pages":"Article 108470"},"PeriodicalIF":5.3,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10561295","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Applications of advanced technologies for detecting genomic structural variation","authors":"Vincent A. Laufer ,&nbsp;Thomas W. Glover ,&nbsp;Thomas E. Wilson","doi":"10.1016/j.mrrev.2023.108475","DOIUrl":"10.1016/j.mrrev.2023.108475","url":null,"abstract":"<div><p>Chromosomal structural variation (SV) encompasses a heterogenous class of genetic variants that exerts strong influences on human health and disease. Despite their importance, many structural variants (SVs) have remained poorly characterized at even a basic level, a discrepancy predicated upon the technical limitations of prior genomic assays. However, recent advances in genomic technology can identify and localize SVs accurately, opening new questions regarding SV risk factors and their impacts in humans. Here, we first define and classify human SVs and their generative mechanisms, highlighting characteristics leveraged by various SV assays. We next examine the first-ever gapless assembly of the human genome and the technical process of assembling it, which required third-generation sequencing technologies to resolve structurally complex loci. The new portions of that “telomere-to-telomere” and subsequent pangenome assemblies highlight aspects of SV biology likely to develop in the near-term. We consider the strengths and limitations of the most promising new SV technologies and when they or longstanding approaches are best suited to meeting salient goals in the study of human SV in population-scale genomics research, clinical, and public health contexts. It is a watershed time in our understanding of human SV when new approaches are expected to fundamentally change genomic applications.</p></div>","PeriodicalId":49789,"journal":{"name":"Mutation Research-Reviews in Mutation Research","volume":"792 ","pages":"Article 108475"},"PeriodicalIF":5.3,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71488118","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}